Practical Administration Information

KEYTRUDA® is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic carcinoma of the oesophagus or HER-2 negative gastroesophageal junction adenocarcinoma in adults whose tumours express PD-L1 with a CPS ≥10.¹

Abbreviations: CPS: combined positive score; HER-2: human epidermal growth factor receptor 2; PD-L1: programmed death-ligand 1.

KEYTRUDA® is reimbursed in line with its indication, in combination with any platinum & fluoropyrimidine based chemotherapy.^*

^*capecitabine-based pharmaceutical specialties and Teysuno^® are not reimbursed in this indication.

Reimbursement wording – French:
Le traitement de première ligne des bénéficiaires adultes atteints d’un cancer de l’œsophage ou d’un adénocarcinome de la jonction gastro-œsophagienne HER-2 négatif, localement avancés non résécables ou métastatiques, dont les tumeurs expriment PD-L1 avec un CPS ≥ 10, en association à une chimiothérapie à base de sels de platine et de fluoropyrimidine (attention : les spécialités pharmaceutiques sur base de capecitabine et la spécialité pharmaceutique Teysuno ne sont pas remboursées dans cette indication).²

Reimbursement wording – Dutch:
De eerstelijnsbehandeling van lokaal gevorderd inoperabel of gemetastaseerd carcinoom van de slokdarm, of HER-2-negatief adenocarcinoom van maag-slokdarm-overgang bij volwassen rechthebbenden bij wie de tumoren PD-L1-expressie vertonen met een CPS ≥ 10, in combinatie met platinum- en fluoropyrimidinebevattende chemotherapie (let op: de farmaceutische specialiteiten op basis van capecitabine en de farmaceutische specialiteit Teysuno worden niet vergoed in deze indicatie).³

Testing for PD-L1 expression

Regardless of squamous cell carcinoma or adenocarcinoma histology, the expression of PD-L1 with a CPS^* ≥10 based on the PD L1 IHC 22C3 clone is required for treatment with KEYTRUDA® + chemotherapy.^1†

^*A minimum of 100 viable tumour cells in the PD-L1–stained slide is required for the specimen to be considered adequate for PD-L1 evaluation.^4
†Platinum and fluoropyrimidine based chemotherapy, capecitabine-based pharmaceutical specialties and Teysuno^® are not reimbursed in this indication.

Abbreviations: CPS: combined positive score; PD-L1: programmed death-ligand 1; 5-FU: fluorouracil.

How do I give KEYTRUDA® in combination with chemotherapy; do I give KEYTRUDA® first?

• KEYTRUDA® must not be given as an intravenous pressure or bolus injection.
• When used in combination, the technical information for the respective accompanying therapeutic agents must be taken into account.
• When KEYTRUDA® is given as part of a combination therapy with intravenous chemotherapy, KEYTRUDA® should be given first.
• Administer the infusion solution intravenously over 30 minutes using a sterile, non-pyrogenic, low-protein binding 0.2 to 5 μm in-line or add-on filter.
• Other drugs must not be given through the same infusion set.
  

Should I reduce the dose of KEYTRUDA® in specific patient subgroups?

• No dose adjustment of KEYTRUDA® is necessary for patients with mild or moderate renal impairment.^1*
• No dose adjustment of KEYTRUDA® is necessary for patients with mild hepatic impairment.^1†

^*KEYTRUDA® has not been studied in patients with severe renal impairment.
^†KEYTRUDA® has not been studied in patients with moderate or severe hepatic impairment.

Example administration scheme

^*Platinum and fluoropyrimidine based chemotherapy, capecitabine-based pharmaceutical specialties and Teysuno^® are not reimbursed in this indication.
^†The information does not claim to be complete; for details on dosage and use, please refer to the relevant specialist product information.
^‡Please note the exact and current approval status of the listed chemotherapeutic agents.

What was the dosing and administration schedule used in the Keynote-590 study?

Do I have flexibility with how I schedule in KEYTRUDA® alongside our chemotherapy regimen? How long should each treatment be given?

Keynote-590 dosing and administration schedule6
KEYTRUDA® 200 mg IV on Day 1 Q3W* in combination with cisplatin 80 mg/m2 IV on Day 1 Q3W† 5-FU 800 mg/m2/day continuous IV infusion on each of Days 1–5 Q3W (total of 4000 mg/m2 per 3-week cycle)‡
The body surface area in m2 should be calculated per local guidance *KEYTRUDA® was administered for 35 cycles (approximately 2 years). †Duration of cisplatin treatment will be capped at 6 cycles. ‡Or per local standard for 5-FU administration duration as long as total dose of 4000 mg/m2 per cycle Q3W is followed. 5-FU treatment is not to exceed a maximum of 35 cycles.

Abbreviations: IV: intravenous; Q3W: every 3 weeks; Q6W: every 6 weeks.

What should I do if my patient has an immune-related adverse event associated with KEYTRUDA®?

Managing adverse reactions:
Please consult SmPC for detailed information regarding the management of adverse events.

Based on the severity and the type of the adverse reaction:

• KEYTRUDA® should be withheld or discontinued to manage adverse reactions. No dose reductions of KEYTRUDA® are recommended.¹
• KEYTRUDA® should be withheld for Grade 2 or Grade 3 events and corticosteroids administered. Upon improvement to Grade ≤1, corticosteroid taper should be initiated and continued over at least 1 month.¹
• Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered.¹
• KEYTRUDA® may be restarted within 12 weeks after last dose of KEYTRUDA® if the adverse reaction recovers to Grade ≤1 and corticosteroid dose has been reduced to ≤10 mg prednisone or equivalent per day.¹
• If treatment-related toxicity does not resolve to Grades 0-1 within 12 weeks after last dose of KEYTRUDA®, or if corticosteroid dosing cannot be reduced to ≤10 mg prednisone or equivalent per day within 12 weeks, KEYTRUDA® should be permanently discontinued.¹
• KEYTRUDA® should be permanently discontinued for Grade 4 or recurrent Grade 3 immune-related adverse reactions, unless otherwise specified in the summary of product characteristics.¹

What should I do if my patient has an infusion-related reaction associated with KEYTRUDA®?

• For Grades 1 or 2 infusion reactions, patients may continue to receive KEYTRUDA® with close monitoring. Premedication with antipyretic and antihistamine may be considered.¹
• For Grades 3 or 4 infusion reactions, infusion should be stopped and KEYTRUDA® permanently discontinued.¹

N.B. For further details please consult the prescribing information.

How can I use KEYTRUDA® with steroids?

• The use of systemic corticosteroids or immunosuppressants before starting KEYTRUDA® should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of KEYTRUDA®.¹
• Systemic corticosteroids or other immunosuppressants can be used after starting KEYTRUDA® to treat immune-related adverse reactions.¹
• Corticosteroids can also be used as premedication, when KEYTRUDA® is used in combination with chemotherapy, as antiemetic prophylaxis and/or to alleviate chemotherapy-related adverse reactions.¹

1. SmPC KEYTRUDA®.
2. Institut national d’assurance maladie-invalidité (INAMI): Médicaments – Keytruda (pembrolizumab) (https://www.inami.fgov.be/fr/programmes-web/Pages/specialites[1]pharmaceutiques.aspx. Accessed on 01/02/22)
3. Website RIZIV: geneesmiddelen – Keytruda (pembrolizumab). (https://www.riziv.fgov.be/nl/toepassingen/Paginas/farmaceutische-specialiteiten.aspx. Accessed on 01/02/22).
4. Agilent Technologies, Inc. Instructions for Use: PD-L1 IHC 22C3 pharmDx
5. Lordick F, et al. Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016;27(Suppl 5):v50–v57.
6. Sun JM, Shen L, Shah MA, et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet 2021(Suppl); 398: 759–71.